A thiazolylimidazole derivative represented by the formula
or a pharmaceutically acceptable salt thereof, and an ALK5 inhibitor, an therapeutic agent for alopecia or a hair growth agent having the above as an active ingredient, wherein:
X
1
and X
2
are different from each other and represent a sulfur atom or a carbon atom; R
1
represents a phenyl group; a substituted phenyl group; a phenyl group condensed with a hetero aromatic ring; a pyridyl group; or a pyridyl group condensed with a hetero aromatic ring; R
2
represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms substituted with 1 to 5 halogen atoms, an alkoxy group having 1 to 6 carbon atoms, an alkanoyl group having 1 to 5 carbon atoms, or a hydroxyalkyl group having 1 to 6 carbon atoms, A represents a group which is represented by the formula.
The present invention provides an inhibitory substance against ALK5 which is a TGF-β type I receptor and provides a hair growth stimulant or a hair growth agent based on its novel activities.
A thiazolylimidazole derivative represented by the formula
or a pharmaceutically acceptable salt thereof, and an ALK5 inhibitor, an therapeutic agent for alopecia or a hair growth agent having the above as an active ingredient,
wherein:
X
1
and X
2
are different from each other and represent a sulfur atom or a carbon atom; R
1
represents a phenyl group; a substituted phenyl group; a phenyl group condensed with a hetero aromatic ring; a pyridyl group; or a pyridyl group condensed with a hetero aromatic ring; R
2
represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkyl group having 1 to 6 carbon atoms substituted with 1 to 5 halogen atoms, an alkoxy group having 1 to 6 carbon atoms, an alkanoyl group having 1 to 5 carbon atoms, or a hydroxyalkyl group having 1 to 6 carbon atoms, A represents a group which is represented by the formula.
The present invention provides an inhibitory substance against ALK5 which is a TGF-β type I receptor and provides a hair growth stimulant or a hair growth agent based on its novel activities.
5-(1,3-Benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazole derivatives as potent and selective transforming growth factor-β type I receptor inhibitors
A series of 5-(1,3-benzothiazol-6-yl)-4-(4-methyl-1,3-thiazol-2-yl)-1H-imidazole derivatives was synthesized as transforming growth factor-beta (TGF-beta) type I receptor (also known as activin-like kinase 5 or ALK5) inhibitors. These compounds were evaluated for their ALK5 inhibitory activity in an enzyme assay and for their TGF-beta-induced Smad2/3 phosphorylation inhibitory activity in a cell-based assay. As a representative compound, 16i was a potent and selective ALK5 inhibitor, exhibiting a good enzyme inhibitory activity (IC50 = 5.5 nM) as well as inhibitory activity against TGF-beta-induced Smad2/3 phosphorylation at a cellular level (IC50 = 36 nM). Furthermore, the topical application of 3% 16i lotion significantly inhibited Smad2 phosphorylation in Mouse skin (90% inhibition compared with vehicle-treated animals). (C) 2012 Elsevier Ltd. All rights reserved.
EP1721905
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公开(公告)日:——
CHEMICALS PROMOTING THE GROWTH OF N-ACYLHOMOSERINE LACTONE-DEGRADING BACTERIA